Inflammatory events based on response to antigens have been implicated in a variety of middle ear disorders including serous otitis media. Investigation of the etiology as well as managment of such disorders as been hampered by a lack of basic knowledge concerning the mechanisms and sequelae of immune responses in the middle ear. An animal model of immune-mediated middle ear effusion and inflammation has been developed, utilizing the guinea pig and keyhole limpet hemocyanin, a potent and extensively studied antigen. This model will be used to further explore the kinetics of middle ear immune responses. This will include contributions of systemic and local mucosal immunity to middle ear immune response and immune-mediated disease. The importance of cell-mediated immunity in the middle ear will also be assessed. The model will be modified to more nearly approximate the conditions seen in human middle ear disease. To this end, antigen dose will be decreased and antigen persistence in the middle ear increased. The importance of various known inflammatory mediators in middle ear effusion and inflammation will be explored by direct assay of effusions and by introduction of extracted and purified mediators into the middle ear cavity. Intervention in immune-mediated middle ear effusion and inflammation will be explored utilizing pharmacologic agents which affect suspected immune and inflammatory pathways. This will both test the feasibility of intervention and also provide information concerning the importance of the targeted inflammatory pathways in immune-mediated middle ear disease.